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Poxvirus attack of anti-viral defense pathways unleashes an effector-triggered NF-κB response

GSE287860 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2025/02/16 Platform GPL24676
Summary
Effector-triggered immunity (ETI) is a form of pathogen sensing that involves detection of pathogen-encoded virulence factors or “effectors”. To discover novel ETI pathways in mammals, we developed a screening approach in which individual virulence factors are expressed in human monocytes and transcriptional responses are assessed by RNA-seq. Using this approach, we identify a poxvirus effector, myxoma virus M3.1, which elicits an anti-viral NF-κB response. We find that NF-κB is unleashed by an ETI pathway that senses M3.1 attack of two anti-viral complexes: ZAP and TBK1. NF-κΒ activation occurs because the proteins inhibited by M3.1—N4BP1, ZC3H12A, and TBK1—are negative regulators of NF-κB. Our results illustrate how negative regulators can function as pathogen sensors and establish a systematic approach for the discovery of ETI pathways.
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Also filed as BioProject PRJNA1214822 and SRA study SRP559545. Searching any of these in the dataset finder brings you back here.

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